DESCRIPTION: (Principal Investigator's) Many, if not most, of the pharmaceutical agents in use today (worldwide) are nitrogen heterocycles. It i unlikely that this situation will change drastically in the next decade, so continuing investigation of new chemistry in such species is warranted, insofa as it provides new methods of synthesis, understanding of chemical reactivities, and novel compounds. The studies outlined in this proposal seek to fully develop recent fundamental discoveries about the chemistry and synthetic utility of lithiated nitrogen heterocycles. The knowledge gained in these studies is expected to enhance our ability to synthesize complex molecules containing nitrogen heterocycles in an efficient manner. One authority has recently asserted that "Reactions with organolithium species as reagents, reactants, or intermediates are so well established that organolithiums are the most widely used organometallics in contemporary organi chemistry" (Beak et al, Acc. Chem. Res. 1996, 29, 552-560). The proposed mechanistic studies will provide basic and fundamental knowledge about a class of organolithiums that are of growing importance to organic synthesis, and tha will have an impact beyond the immediate questions posed herein. The specific aims of this proposal are to: (1) Continue investigation of the scope and limitations of alpha-aminoorganolithium alkylations and sigmatropic rearrangements, with emphasis on stereoselectivity. Develop improved methods o preparation. (2) Apply the sigmatropic rearrangement of N-allyl-2-lithio heterocycles to the synthesis of aza sugars and potential glycosidase inhibitors. (3) Using spectroscopic and cryoscopic techniques, characterize th solution structure of unstabilized alpha-aminoorganolithium species. Attempt t grow crystals for X-ray diffraction analysis. (4) Test the hypothesis that the reason for occasional nonselective reaction of alpha-aminoorganolithiums is du to the intervention of single electron transfer processes.